A Study Using Available Data to Learn to What Extent Patients With Prostate Cancer Who Received Second Generation Androgen Receptor Inhibitors Took Their Medication as Prescribed or Stopped Taking Their Medication Completely

Medication Adherence and Discontinuation Among Patients With Prostate Cancer Who Initiated Second Generation Androgen Receptor Inhibitors

This is an observational study in which patient data from the past on men with prostate cancer are studied.

Cancer is a condition in which the body cannot control the growth of cells and tumors may form. If tumors form in the prostate, male sex hormones (androgens) can sometimes help the cancer spread and grow. Cancer that spreads to other parts of the body is called metastasis.

Androgens are mainly made in the testicles. There are treatments available for men with prostate cancer to lower the levels of these hormones in the body. These treatments are called androgen deprivation therapy (ADT). Some men with prostate cancer respond to ADT, but in some cases, prostate cancer may overcome the therapy and worsen despite low androgens levels.

Second generation androgen receptor inhibitors (SGARIs) including darolutamide, apalutamide, and enzalutamide are available for the treatment of prostate cancer in addition to ADT. SGARIs work by blocking androgens from attaching to proteins in cancer cells in the prostate.

Clinical studies have shown that men with prostate cancer benefit from these treatments. But besides benefits, unfavorable reactions related to these treatments also influence which treatment is chosen, if the treatment is taken as intended or if it is even stopped.

Unfavorable reactions observed for darolutamide, apalutamide, and enzalutamide differ from each other. In clinical trials, severe unfavorable reactions occurred less often for darolutamide.

But information on how unfavorable reactions of each treatment influence their intake in actual or "real-world" prostate cancer treatment is missing.

The main aim of this observational study is to learn to what extent SGARI treatments are taken as prescribed and how often their intake is completely stopped. To find this out, researchers will collect available treatment data of adult men with prostate cancer from the United States who started SGARI treatments between August 2019 and March 2021. The data will be drawn from the IQVIA database.

For each man, data from up to 1 year prior SGARI treatment until at least 3 months after treatment start (up to the 30 June 2021) will be collected.

The researchers will look at the percentage of men who:

• completely stopped to take their treatment or
• took the treatment as prescribed.

The results for each treatment (darolutamide, apalutamide, and enzalutamide) will then be compared to find possible differences.

There will be no required visits with a study doctor or required tests in this study since only patient data from the past are studied.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Darolutamide (Nubeqa, BAY1841788); Drug: Enzalutamide; Drug: Apalutamide

• Study Type: Observational
• Enrollment (Actual): 13779

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Whippany, New Jersey, United States, 07981
      • Bayer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients diagnosed with Prostate Cancer who newly initiate Second Generation Androgen Receptor Inhibitors treatment in United States from 01 Aug 2019 to 31 Mar 2021.

Description

Inclusion Criteria:

• Have at least 1 prescription claims for enzalutamide (National Drug Code [NDC]: 00469-0125-99, 00469-0625-99, 00469-0725-60), apalutamide (NDC: 59676-600-12, 59676-600-56, 59676-600-99) or darolutamide (NDC: 50419-395-01, 50419-395-72) during the index identification period.

  -- The date of the earliest SGARI claim to occur during this period will be defined as the index date with the corresponding SGARI as the index treatment.

• Have ≥1 diagnosis of prostate cancer (ICD-10 code C61.) during the overall baseline period.
• Age ≥18 years and male gender on the index date.
• Have continuous health plan enrollment with medical and pharmacy benefits for at least 6 months prior to the index date.
• Have continuous health plan enrollment with medical and pharmacy benefits for at least 3 months after the index date and throughout the follow-up period.

Exclusion Criteria:

• Since patients should not be prescribed more than one SGARI when initiating treatment, patients with more than one SGARI prescribed on the index date will be excluded from the study. This will allow each patient to be assigned to a single study cohort.
• In order to select patients who are initiating SGARI treatment, patients with the index SGARI treatment during the 1 year baseline period will be excluded from the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Darolutamide cohort (Daro); Participants received Second Generation Androgen Receptor Inhibitor (SGARI) Darolutamide as initial treatment	Drug: Darolutamide (Nubeqa, BAY1841788); Retrospective cohort analysis, using the IQVIA Real-World Data Adjudicated Claims, US claims database
Enzalutamide cohort (Enza); Participants received Second Generation Androgen Receptor Inhibitor (SGARI) Enzalutamide as initial treatment	Drug: Enzalutamide; Retrospective cohort analysis, using the IQVIA Real-World Data Adjudicated Claims, US claims database
Apalutamide cohort (Apa); Participants received Second Generation Androgen Receptor Inhibitor (SGARI) Apalutamide as initial treatment	Drug: Apalutamide; Retrospective cohort analysis, using the IQVIA Real-World Data Adjudicated Claims, US claims database

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Discontinuation rate of SGARI treatment	The proportion of patients who discontinue their index SGARI treatment at 3 months, 6 months, 1 year and acutely (discontinuation within 90 days) will be evaluated. In addition, time to discontinuation will be assessed. Discontinuation will be defined as a gap of ≥60 days from the end of the days of supply (DOS) of a prescription claim for the index SGARI to the date of the next prescription claim. The date of the last day of supply for the prescription claim that occurs immediately prior to the gap will be defined as the date of discontinuation. Discontinuation rate will be defined as the proportion of patients with discontinuation within a set time period (3 months, 6 months, 1 year).	Retrospective analysis from index date 01-Aug-2019 up to 30-Jun-2021
Time to discontinuation (days) of SGARI treatment	Time to discontinuation will be assessed over the entire observation period	Retrospective analysis from index date 01-Aug-2019 up to 30-Jun-2021
Adherence of SGARI treatment	Medication adherence will be assessed using medication possession ratio (MPR) and proportion of days covered (PDC)	Retrospective analysis from index date 01-Aug-2019 up to 30-Jun-2021

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment duration of SGARI treatment	Continuous treatment duration will be defined as the number of days from the index date to the date of discontinuation or the censoring date, whichever is earlier	Retrospective analysis from index date 01-Aug-2019 up to 30-Jun-2021
Risk factors for treatment discontinuation	Sociodemographic and clinical patient characteristics will be assessed to identify risk factors associated with the discontinuation of index SGARI treatment using multivariable logistic regression models.	Retrospective analysis from index date 01-Aug-2019 up to 30-Jun-2021
The proportion of patients who had evidence of dose modification of their index SGARI treatment	Dose modifications will be measured using relative dose intensity (RDI) calculated as the ratio of the delivered dose intensity to the standard dose intensity as recommended for each SGARI	Retrospective analysis from index date 01-Aug-2019 up to 30-Jun-2021
Time to first dose modification (days) of index SGARI treatment		Retrospective analysis from index date 01-Aug-2019 up to 30-Jun-2021
Descriptive summary of the baseline demographics of Prostate Cancer (PC) patients treated with SGARIs	Patient demographics evaluated on the index date will consist of age, race, region, insurance and health plan type when available	Retrospective analysis during index identification period, from 01-Aug-2018 up to 31-Mar-2021
Descriptive summary of the Comorbid conditions	For each qualified patient, the twelve-month baseline period or on the index date will be examined in order to compile patient histories	Retrospective analysis from 01-Aug-2018 up to 31-Mar-2021
Descriptive summary of the Charlson Comorbidity Index (CCI)	Charlson Comorbidity Index (CCI): The CCI is a method of estimating the one-year mortality for a patient with certain comorbid conditions. Each comorbid condition is given a score of 1, 2, 3 or 6 based on the degree of mortality attributed to the condition. The scores are summed to yield a total index score which can be used to predict long-term survival. The CCI will be calculated for each patient based on all diagnoses during the 1 year baseline period and the index date	Retrospective analysis from 01-Aug-2018 up to 31-Mar-2021
The proportion of patients who received different PC related medications	PC related medications: Androgen Deprivation Therapy (ADT) alone; First-generation antiandrogens; Second-generation androgen receptor inhibitors (SGARI); Chemotherapy; Other chemotherapy; Immunotherapy; Bone health agents; Radiopharmaceutical	Retrospective analysis from 01-Aug-2018 up to 30-Jun-2021
Descriptive summary of the baseline SGARI-class exposure status	SGARI-class exposure status: SGARI-class naïve; SGARI-class experienced	Retrospective analysis from 01-Aug-2018 up to 31-Mar-2021
Descriptive summary of the baseline Hormone sensitivity status	Hormone sensitivity status: Hormone-sensitive PC; Castration-resistant PC; Unknown	Retrospective analysis from 01-Aug-2018 up to 31-Mar-2021

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here for access to information about Bayer's transparency standards and Bayer studies

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2022
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: January 10, 2022
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 21, 2022

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 29, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 22053

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No